Actinoallolides A-E (1-5) are new 12-membered anti-trypanosomal macrolides, isolated from a cultured broth of Actinoallomurus fulvus MK10-036 during our program of physicochemical screening for metabolites. The absolute configuration of Actinoallolide A (1) was determined by detailed NMR analyses and single-crystal X-ray crystallography of its MTPA ester .The structural features of 1 are as follows; 1) a 12-membered macrolactone possessing 5-membered hemiacetal moiety inside the macrolactone ring, and 2) a side chain including consecutive asymmetric centers, which can be recognized by the similarly repeating stereo-chemical triad embedded in the linear backbone. In previous our isolation study and structural analysis of Actinoallolides indicated that the hemiacetal moiety would easily undergo β-elimination of the hydroxy group at the C-3 position under acidic conditions to afford enone-type Actinoallolides C (3) and D (4). In addition, the acid-sensitive hemiacetal moiety could be led from the β-ketoester precursor, which is highly reactive moiety under acidic and basic conditions. Hence, we needed to develop selective preparation of the hemiacetal moiety from a β-ketoester at the late stage to complete the total synthesis. The remark mentioned above, we envisaged that utilizing a stable phenolether as a key precursor for construction of a highly reactive hemiacetal moiety could overcome possible instability toward the total synthesis of 1. In this poster, we describe the synthesis of a key linear intermediate (9) as essential all carbon framework for complete the convergent total synthesis of Actinoallolide A (1).

Towards the total synthesis of the anti-trypanosomal macrolide, actinoallolides: Construction of a key linear intermediate

251st National Meeting (2016)

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